KineTACs Design and Development Service

Our service offers a cutting-edge solution for targeted degradation of extracellular and membrane-associated proteins, using cytokine-antibody fusion molecules known as KineTACs (Cytokine-based Targeting Chimeras). KineTACs harness the endocytic pathways of cytokine receptors to internalize and degrade disease-related targets, providing a novel therapeutic mechanism that complements and extends beyond traditional Proteolysis-targeting Chimera and LYTAC platforms. By integrating computational protein design, cytokine engineering, and cell-based functional validation, we accelerate the development of efficient, selective, and biologically active KineTACs molecules for both drug discovery and mechanistic studies.

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Core Capabilities

Computational Protein Design and Docking
- Predictive modeling of cytokine–receptor and antibody–antigen interactions.
- Linker length and fusion site optimization for balanced binding affinity and degradation efficiency.
Cytokine–Antibody Fusion Construction
- Fusion of engineered cytokines (e.g., IL-2, IL-4, GM-CSF) to antibodies or antibody fragments targeting disease-relevant extracellular proteins.
- Expression in mammalian or CHO systems for optimal folding and glycosylation.
Molecular and Functional Characterization
- Binding affinity testing (SPR, BLI).
- Internalization assays to confirm cytokine receptor-mediated uptake.
- Degradation verification via western blot or ELISA.
Cell-Based Degradation and Trafficking Assays
- Quantitative assessment of target protein reduction in relevant cell lines.
- Imaging-based validation of lysosomal localization.
Optimization and Scalability
- Mutagenesis and structure-guided tuning of cytokine activity to balance efficacy and safety.
- Scale-up expression and purification for preclinical evaluation.

Applications

Area	Example Applications
Oncology	Degradation of tumor-promoting membrane receptors and ligands.
Immunology	Targeting cytokine receptors or immune checkpoint proteins.
Neurodegenerative Diseases	Clearance of neurotoxic extracellular proteins.
Autoimmune Diseases	Modulation of overactive immune signaling pathways.
Therapeutic Antibody Validation	Exploring extracellular degradation as an alternative therapeutic mechanism.

Key Advantages

Expands the scope of targeted protein degradation beyond intracellular targets.
No reliance on lysosomal receptor ligands-leverages native cytokine receptor endocytosis.
Customizable fusion architectures for diverse target classes.
High specificity and controlled cytokine signaling activity.
Compatible with humanized or Fc-silenced antibody formats.

Deliverables

Designed and validated KineTACs fusion constructs.
Expression and purification reports.
Functional binding and degradation data.
Optional in vitro or in vivo validation studies.

Comparison of Targeted Protein Degradation Platforms

Feature	Cytokine-based Targeting Chimeras	Lysosome-Targeting Chimeras	Proteolysis Targeting Chimeras
Primary Target Space	Extracellular and membrane-bound proteins	Extracellular and membrane-bound proteins	Intracellular proteins
Mechanism of Action	Leverages cytokine receptor-mediated endocytosis to internalize and degrade target proteins via lysosomal pathways	Utilizes lysosome-shuttling receptors (e.g., CI-M6PR, ASGPR) to transport target proteins for lysosomal degradation	Uses E3 ubiquitin ligase recruitment to mark target proteins for proteasomal degradation
Molecular Architecture	Cytokine–antibody fusion protein that binds both target and cytokine receptor	Bifunctional molecule linking target binder (antibody/small molecule) to lysosomal receptor ligand	Bifunctional small molecule linking target ligand to E3 ligase ligand
Uptake Pathway	Cytokine receptor internalization (e.g., IL-2R, GM-CSFR)	Lysosomal receptor-mediated endocytosis	Intracellular ubiquitin–proteasome system
Subcellular Destination	Lysosome	Lysosome	Proteasome
Target Classes	Membrane receptors, secreted cytokines, extracellular enzymes	Membrane receptors, secreted proteins	Transcription factors, kinases, enzymes
Molecule Type	Large biologic (~100–150 kDa fusion protein)	Large biologic or conjugate (~100–200 kDa)	Small molecule (<1 kDa)
Design Complexity	Moderate (cytokine–antibody fusion, linker engineering)	Moderate to high (ligand–receptor pair matching, linker optimization)	High (ligase selection, linker optimization, cell permeability)
Selectivity & Tunability	High selectivity; tunable cytokine activity and receptor choice	High selectivity; dependent on receptor expression	Dependent on E3 ligase expression and target engagement
Delivery Requirements	Protein therapeutic delivery (IV or SC)	Protein or conjugate delivery (IV)	Cell-permeable small molecule delivery (oral or IV)
Advantages	Utilizes native cytokine pathways for internalization No lysosomal receptor dependency Enables extracellular target degradation	Expands degradation to non-internalizing extracellular targets Modular design using known lysosomal receptors	Well-established technology High intracellular efficiency Reversible and catalytic mechanism
Limitations	Limited to cells expressing cytokine receptors Requires careful cytokine tuning to minimize off-target signaling	Restricted by receptor expression profile Complex conjugate synthesis	Limited to intracellular proteins Potential off-target ubiquitination
Stage of Development	Emerging (preclinical proof-of-concept)	Emerging (preclinical validation)	Established (multiple clinical candidates)

Why Choose Us

With expertise spanning cytokine biology, protein engineering, and structural modeling, our team delivers a comprehensive KineTACs development workflow-from in silico design to experimental validation. Our customized approach ensures high-affinity fusion molecules that effectively degrade extracellular targets, supporting the development of next-generation biologic therapeutics.

* For Research Use Only.

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